Melanoma is the deadliest form of skin cancer and has the fastest growth rate of all cancer types. In the U.S., the lifetime risk is about 1 in 55, while other parts of the world have even greater risks. Early surgical resection of melanoma is the best avenue of therapy. However, for those cases where the lesion progresses and spreads, monitoring of metastatic disease is crucial for positive clinical outcomes. This proposal uses photoacoustics, or laser induced ultrasound, to detect circulating melanoma cells (CMC's) in blood. This method will exploit the natural light absorber, melanin, within the cells providing a simple, sensitive, and label free means to monitor metastasis. In this method, mononuclear cells obtained from blood are irradiated with a rapid pulsed tunable laser system in a set up similar to flow cytometry. If there are CMC's present in whole blood, they will reside among the mononuclear cells. While a mononuclear cell will not absorb light at visible wavelengths, CMC's will selectively absorb the optical energy and become active acoustic sources, creating transient, high frequency pressure waves that are the signature of CMC's. This proposal has two focus areas: 1) Improve the current detection system, and 2) Use a mouse melanoma model to study the time course of metastasis and its relationship to the presence of CMC's. In order to improve the current system, a focused acoustic sensor will be set within a modified flow chamber. This improvement will mitigate alignment difficulties and decrease spurious noise. Real time wavelet denoising using an automated algorithm will be incorporated. Finally, a statistical classification scheme to discriminate melanoma cells from red blood cells will be incorporated, thus improving specificity of the test. A metastatic melanoma mouse model to study how the presence of CMC's correlate to tumor load and disease state will be studied. Metastasis will be induced in 50 mice and micro-CT coregistered with micro-PET will be performed to monitor tumor load. The mice will be sacrificed and exsanguinated on a schedule determined by calculated tumor size and perform the photoacoustic tests. This research will be used to design optimal schedules for CMC testing in human patients. The information given by monitoring CMC's will be used to detect metastasis, relapse, remission, and response to therapy. No other system is available to offer such information. PUBLIC HEALTH RELEVANCE: Detection of circulating tumor cells in human blood allows clinicians to observe metastasis and monitor cancer therapy in their patients. Using melanins inherent optical absorption to detect laser induced acoustic waves in melanoma cells, a system will be designed for rapid detection of those cells. Results from testing the system on a mouse melanoma model will be used to design an optimal testing plan for human cancer patients.